Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20027 | 60304;60305;60306 | chr2:178591740;178591739;178591738 | chr2:179456467;179456466;179456465 |
| N2AB | 18386 | 55381;55382;55383 | chr2:178591740;178591739;178591738 | chr2:179456467;179456466;179456465 |
| N2A | 17459 | 52600;52601;52602 | chr2:178591740;178591739;178591738 | chr2:179456467;179456466;179456465 |
| N2B | 10962 | 33109;33110;33111 | chr2:178591740;178591739;178591738 | chr2:179456467;179456466;179456465 |
| Novex-1 | 11087 | 33484;33485;33486 | chr2:178591740;178591739;178591738 | chr2:179456467;179456466;179456465 |
| Novex-2 | 11154 | 33685;33686;33687 | chr2:178591740;178591739;178591738 | chr2:179456467;179456466;179456465 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | None | None | 1.0 | N | 0.751 | 0.465 | 0.458554320643 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| F/L | rs1184403397  |
-1.022 | 0.98 | N | 0.519 | 0.396 | 0.413113201963 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| F/L | rs1184403397 |
-1.022 | 0.98 | N | 0.519 | 0.396 | 0.413113201963 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/L | rs1184403397 |
-1.022 | 0.98 | N | 0.519 | 0.396 | 0.413113201963 | gnomAD-4.0.0 | 3.09937E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39101E-06 | 0 | 1.60128E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8467 | likely_pathogenic | 0.8846 | pathogenic | -2.185 | Highly Destabilizing | 0.993 | D | 0.655 | neutral | None | None | None | None | N |
| F/C | 0.4579 | ambiguous | 0.5215 | ambiguous | -1.344 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.432172113 | None | None | N |
| F/D | 0.9545 | likely_pathogenic | 0.9702 | pathogenic | -1.204 | Destabilizing | 0.999 | D | 0.79 | deleterious | None | None | None | None | N |
| F/E | 0.9382 | likely_pathogenic | 0.9584 | pathogenic | -1.067 | Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | N |
| F/G | 0.9326 | likely_pathogenic | 0.9523 | pathogenic | -2.559 | Highly Destabilizing | 0.998 | D | 0.719 | prob.delet. | None | None | None | None | N |
| F/H | 0.6224 | likely_pathogenic | 0.686 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| F/I | 0.4856 | ambiguous | 0.5351 | ambiguous | -1.034 | Destabilizing | 0.999 | D | 0.625 | neutral | N | 0.436999143 | None | None | N |
| F/K | 0.9474 | likely_pathogenic | 0.9644 | pathogenic | -1.523 | Destabilizing | 0.999 | D | 0.792 | deleterious | None | None | None | None | N |
| F/L | 0.952 | likely_pathogenic | 0.9618 | pathogenic | -1.034 | Destabilizing | 0.98 | D | 0.519 | neutral | N | 0.402443852 | None | None | N |
| F/M | 0.7416 | likely_pathogenic | 0.7884 | pathogenic | -0.823 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| F/N | 0.8438 | likely_pathogenic | 0.8968 | pathogenic | -1.752 | Destabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | N |
| F/P | 0.9958 | likely_pathogenic | 0.9977 | pathogenic | -1.415 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| F/Q | 0.8927 | likely_pathogenic | 0.9225 | pathogenic | -1.717 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| F/R | 0.9088 | likely_pathogenic | 0.9355 | pathogenic | -0.991 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| F/S | 0.7818 | likely_pathogenic | 0.8381 | pathogenic | -2.526 | Highly Destabilizing | 0.999 | D | 0.748 | deleterious | N | 0.457086413 | None | None | N |
| F/T | 0.8513 | likely_pathogenic | 0.8926 | pathogenic | -2.285 | Highly Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | N |
| F/V | 0.4589 | ambiguous | 0.5177 | ambiguous | -1.415 | Destabilizing | 0.999 | D | 0.673 | neutral | N | 0.374065172 | None | None | N |
| F/W | 0.4818 | ambiguous | 0.557 | ambiguous | -0.099 | Destabilizing | 0.171 | N | 0.305 | neutral | None | None | None | None | N |
| F/Y | 0.1103 | likely_benign | 0.1248 | benign | -0.408 | Destabilizing | 0.98 | D | 0.527 | neutral | N | 0.439116728 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.